2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004070543v1 16/2/417    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bushinsky, D. A. Articles by Asplin, J. R. Search for Related Content PubMed PubMed Citation Articles by Bushinsky, D. A. Articles by Asplin, J. R. Related Collections Related Article

Thiazides Reduce Brushite, but not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone–Forming Rats

David A. Bushinsky^* and John R. Asplin

^* Nephrology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York; and Section of Nephrology, Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois

Address correspondence to: Dr. David A. Bushinsky, Department of Medicine, University of Rochester School of Medicine and Dentistry, Strong Memorial Hospital, 601 Elmwood Avenue, Box 675, Rochester, NY 14642. Phone: 585-275-3660; Fax: 585-442-9201; E-mail: david_bushinsky{at}urmc.rochester.edu

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone–forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.

Related Article

This Month’s Highlights
J. Am. Soc. Nephrol. 2005 16: 279-283. [Full Text] [PDF]

This article has been cited by other articles:

				R. R. Hoopes Jr., F. A. Middleton, S. Sen, P. A. Hueber, R. Reid, D. A. Bushinsky, and S. J. Scheinman Isolation and Confirmation of a Calcium Excretion Quantitative Trait Locus on Chromosome 1 in Genetic Hypercalciuric Stone-Forming Congenic Rats J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1292 - 1304. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673